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Lyophilization Validation: Process Qualification and Continued Process Verification

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Principles and Practices of Lyophilization in Product Development and Manufacturing

Part of the book series: AAPS Advances in the Pharmaceutical Sciences Series ((AAPS,volume 59))

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Abstract

This work describes the lyophilization process validation and consists of two parts. Part I (Part I: Process Design and Modeling) focuses on the process design and is described in the previous paper, while the current paper is devoted to process qualification and continued process verification. The goal of the study is to show the cutting edge of lyophilization validation based on the integrated community-based opinion and the industrial perspective.

This study presents best practices for batch size determination and includes the effect of batch size on drying time, process parameters selection strategies, and batch size overage to compensate for losses during production. It also includes sampling strategies to demonstrate batch uniformity as well as the use of statistical models to ensure adequate sampling.

Based on the LyoHUB member organizations survey, the best practices in determining the number of PPQ runs are developed including the bracketing approach with minimum and maximum loads. Standard practice around CQA and CPP selection is outlined and shows the advantages of using control charts and run charts for process trending and quality control.

The case studies demonstrating the validation strategy for monoclonal antibody and the impact of the loading process on the lyophilization cycle and product quality as well as the special case of lyophilization for dual-chamber cartridge system are chosen to illustrate the process validation. The standard practices in the validation of the lyophilization process, special lyophilization processes, and their impact on the validation strategy are discussed.

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Change history

  • 09 August 2023

    A correction has been published.

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Acknowledgments

We thank Andrea Allmendinger (Roche), Melissa Bentley (BMS), Bakul Bhatnagar (Pfizer), Dilbir Bindra (BMS), Xiaodong Chen (BMS), Dan Dixon (Pfizer), Reza Eivaskhani (Janssen), Pierre Goldbach (Roche), Frank Kanka (Pfizer), Sumit Luthra (Pfizer), Marjoh Nauta (Pfizer), David Ochsenbein (Janssen), Ekneet Sahni (Pfizer), James Searles (Pfizer), Justin Stanbro (Merck & Co., Inc.), David Hamilton (Merck &Co., Inc.), Zak Yusoff (SP Scientific), and LyoHub members for the critical review of the manuscript and their valuable comments.

Funding Statement (Section J)

Alina Alexeenko: Paid employee of LyoHUB, Purdue University, at the time of the project/paper drafting process.

Joe Azzarella: N/A.

Akhilesh Bhambhani: N/A.

Rui Fang: N/A.

Lavanya Iyer: N/A.

Feroz Jameel: N/A.

Mehfouz Jalal: Paid employee of LyoHUB, Purdue University, at the time of the project/paper drafting process.

Petr Kazarin: Paid employee of LyoHUB, Purdue University, at the time of the project/paper drafting process.

Lokesh Kumar: N/A.

Sumit Luthra: N/A.

Ehab Moussa: No sponsorship or sources of material not available commercially are applicable.

Greg Sacha: N/A.

Puneet Sharma: No sponsorship or sources of material not available commercially are applicable, during his time at Genentech.

Jayasree Srinivasan: N/A.

Serguei Tchessalov: All presented work was performed internally and funded by Pfizer.

Ted Tharp: N/A.

Tong Zhu: No specific funding is provided (on Abbvie side) for the authors’ contribution to this paper.

Conflict of Interest (Section K)

Alina Alexeenko: Proprietary work with Janssen

Joe Azzarella: No

Akhilesh Bhambhani: No

Rui Fang: No

Lavanya Iyer: No

Feroz Jameel: No

Mehfouz Jalal: No

Petr Kazarin: No

Lokesh Kumar: No

Sumit Luthra: No

Ehab Moussa: No

Greg Sacha: No

Puneet Sharma: No

Jayasree Srinivasan: No

Serguei Tchessalov: No

Ted Tharp: No

Tong Zhu: No

Author Contributions (Section L)

Alina Alexeenko: Substantial contributions to the conception or design of the work or the acquisition, analysis, or interpretation of data for the work; drafting the work or revising it critically for important intellectual content; final approval of the version to be published; and agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Joe Azzarella: Revised the drafted works and assisted in ensuring that questions related to the accuracy or integrity of any part of the work were appropriately investigated and resolved.

Akhilesh Bhambhani: Substantial contributions to the conception or design of the work or the acquisition, analysis, or interpretation of data for the work; drafting the work or revising it critically for important intellectual content; final approval of the version to be published; and agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. Accountable for the work and end to end.

Rui Fang: Substantial contributions to the conception or design of the work or the acquisition, analysis, or interpretation of data for the work; drafting the work or revising it critically for important intellectual content; final approval of the version to be published; and agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. Accountable for the work and end to end.

Lavanya Iyer: Contributed to the acquisition and interpretation of data for the work and authoring and revising the draft. Accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Feroz Jameel: Substantial contributions to the conception or design of the work or the acquisition, analysis, or interpretation of data for the work; drafting the work or revising it critically for important intellectual content; and agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Mehfouz Jalal: Responsible for consolidating the information contributed by all the authors and compiling it into a cohesive single document. He was also responsible for editing the contents of the contributions and discussing with authors regarding the information they provided for its clarity.

Petr Kazarin: Responsible for consolidating the information contributed by all the authors and compiling it into a cohesive single document. He was also responsible for editing the contents of the contributions and discussing with authors regarding the information they provided for its clarity.

Lokesh Kumar: For Paper I, led and drafted the Controlled Ice Nucleation section. Also, did review of other section(s) and final approval of the version to be published.

Sumit Luthra: Contributed to drafting the work and revising it critically for important intellectual content.

Ehab Moussa: Substantial contributions to the conception or design of the work or the acquisition, analysis, or interpretation of data for the work; drafting the work or revising it critically for important intellectual content; and final approval of the version to be published

Greg Sacha: Authored Sections 3 and 5 for Paper 1 and provided information and data for Paper 2.

Puneet Sharma: Paper 1: Contributed as an author/reviewer for the following sections: Generation and use of design space, and Engineering/development runs at scale. Paper 2: Contributed as an author/reviewer for following sections: PPQ protocol, recommended analytical testing (discussion of differences in pCQAs of small molecules, biotherapeutics, and vaccines), and continued process verification.

Jayasree Srinivasan: Substantial contributions to the conception or design of the work or the acquisition, analysis, or interpretation of data for the work; drafting the work or revising it critically for important intellectual content; final approval of the version to be published; and agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Serguei Tchessalov: In Paper 1, contributed to the concept of paper, participated in paper outlines, and reviewed final content. In Paper 2, co-author section on validation of lyo processes in alternative containers (dual chamber containers and trays), participated in paper discussions, and reviewed final content.

Ted Tharp: Involved in the original conceptual efforts of topics of interest for the paper, leading and contributing to a number of the subsections and in the review and revision process.

Tong Zhu: Substantial contributions to the conception or design of the work or the acquisition, analysis, or interpretation of data for the work; drafting the work or revising it critically for important intellectual content; final approval of the version to be published; and agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Author information

Authors and Affiliations

  1. AbbVie, North Chicago, IL, USA

    Feroz Jameel, Tong Zhu, Ehab Moussa & Ted Tharp

  2. Purdue University, West Lafayette, IN, USA

    Alina Alexeenko & Petr Kazarin

  3. Merck, Rahway, NJ, USA

    Akhilesh Bhambhani

  4. Baxter, Deerfield, IL, USA

    Gregory Sacha & Jayasree Srinivasan

  5. Pfizer, New York, NY, USA

    Serguei Tchessalov & Sumit Luthra

  6. Genentech, South San Francisco, CA, USA

    Puneet Sharma

  7. BMS, New York, NY, USA

    Lavanya Iyer

  8. Fresenius Kabi, Buffalo, NY, USA

    Joseph Azzarella

  9. IMA Life, Tonawanda, NY, USA

    Mehfouz Jalal

Authors
  1. Feroz Jameel
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  2. Alina Alexeenko
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  4. Gregory Sacha
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  5. Tong Zhu
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  6. Serguei Tchessalov
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  7. Puneet Sharma
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  8. Ehab Moussa
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  9. Lavanya Iyer
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  10. Sumit Luthra
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  11. Jayasree Srinivasan
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  12. Ted Tharp
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  13. Joseph Azzarella
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  14. Petr Kazarin
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  15. Mehfouz Jalal
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Editor information

Editors and Affiliations

  1. Nimble BioSolutions, Gurnee, IL, USA

    Feroz Jameel

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Jameel, F. et al. (2023). Lyophilization Validation: Process Qualification and Continued Process Verification. In: Jameel, F. (eds) Principles and Practices of Lyophilization in Product Development and Manufacturing . AAPS Advances in the Pharmaceutical Sciences Series, vol 59. Springer, Cham. https://doi.org/10.1007/978-3-031-12634-5_27

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